Mentions:
Our data indicate that IL-27-induced NFIL3 plays a key role in the induction of Tim-3 and IL-10 in effector T cells and increases dysfunctional phenotype in effector CD4+ T cells. We therefore hypothesized that overexpression of NFIL3 could dampen effector T cell function. Thus, we transduced naïve CD4+ T cells with NFIL3-expressing retrovirus (NFIL3) and transferred these cells into Rag1−/−13 recipient mice and observed these mice for the development of gut inflammation. Recipient mice that received NFIL3-transduced CD4+ T cells failed to develop wasting disease 10 weeks after transfer (Fig. 6a), when compared with the control mice that received empty virus-transduced (GFP) CD4+ T cells. Histological analysis further revealed that empty virus-transduced T cells induced significantly higher mucosal inflammation than NFIL3 transduced T cells. After grading the crypt damage and cell infiltration (as described in Supplementary Fig. 8a), we observed that almost all of the recipient mice that received empty virus-transduced CD4+ T cells developed clear histological signs of both enteritis and colitis. In contrast, about half of the mice transferred with NFIL3-transduced T cells did not have any signs of gut inflammation and the rest of the mice had a milder inflammation when compared to the mice transferred with control empty virus-transduced T cells (Fig. 6b). We also found that NFIL3-transduced T cells were localized in Peyer’s patches, suggesting that failure to induce inflammation in the gut was not due to a defect of cell migration (Supplementary Fig. 8b). In addition, when we harvested empty virus- and NFIL3-transduced cells from the mesenteric lymph nodes of recipient mice 6 weeks post transfer, we found that NFIL3-transduced cells exhibited high Tim-3 expression and IL-10 production, but low IFN-γ production. Although not statistically significant, a clear trend towards low IL-2 production was also observed (Fig. 6c). Collectively, these data indicate that the effector function of NFIL3-transduced CD4+ T cells was suppressed in vivo, thereby attenuating the induction of gut inflammation.

Mentions:
Our data indicate that IL-27-induced NFIL3 plays a key role in the induction of Tim-3 and IL-10 in effector T cells and increases dysfunctional phenotype in effector CD4+ T cells. We therefore hypothesized that overexpression of NFIL3 could dampen effector T cell function. Thus, we transduced naïve CD4+ T cells with NFIL3-expressing retrovirus (NFIL3) and transferred these cells into Rag1−/−13 recipient mice and observed these mice for the development of gut inflammation. Recipient mice that received NFIL3-transduced CD4+ T cells failed to develop wasting disease 10 weeks after transfer (Fig. 6a), when compared with the control mice that received empty virus-transduced (GFP) CD4+ T cells. Histological analysis further revealed that empty virus-transduced T cells induced significantly higher mucosal inflammation than NFIL3 transduced T cells. After grading the crypt damage and cell infiltration (as described in Supplementary Fig. 8a), we observed that almost all of the recipient mice that received empty virus-transduced CD4+ T cells developed clear histological signs of both enteritis and colitis. In contrast, about half of the mice transferred with NFIL3-transduced T cells did not have any signs of gut inflammation and the rest of the mice had a milder inflammation when compared to the mice transferred with control empty virus-transduced T cells (Fig. 6b). We also found that NFIL3-transduced T cells were localized in Peyer’s patches, suggesting that failure to induce inflammation in the gut was not due to a defect of cell migration (Supplementary Fig. 8b). In addition, when we harvested empty virus- and NFIL3-transduced cells from the mesenteric lymph nodes of recipient mice 6 weeks post transfer, we found that NFIL3-transduced cells exhibited high Tim-3 expression and IL-10 production, but low IFN-γ production. Although not statistically significant, a clear trend towards low IL-2 production was also observed (Fig. 6c). Collectively, these data indicate that the effector function of NFIL3-transduced CD4+ T cells was suppressed in vivo, thereby attenuating the induction of gut inflammation.